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Biomedical subjects

L Tang

Publications and source records attributed to L Tang.

At least 163 records · Page 9Linked to original sources
PubMed1998

Structure of a snake venom phospholipase A2 modified by p-bromo-phenacyl-bromide.

The crystal structure of acidic phospholipase A2 (APLA2) from Agkistrodon halys pallas covalently modified by p-bromo-phenacyl-bromide (pBPB) was determined to a resolution of 2.0 A by an isomorphous difference Fourier method with the native APLA2 structure as an initial model and refined to a crystallographic R factor of 15.3%. The modified APLA2 structure is remarkably similar to that of the native one. Least-squares superposition of C alpha atoms of native and modified APLA2 results in a root-mean-square coordinate deviation of 0.243 A. The p-bromo-phenacyl group near the active site occupies a position similar to that in pBPB modified bovine pancreatic PLA2. The inhibitor covalently bound to the NDI atom of His48 fits well in the hydrophobic channel, forming extensive hydrophobic interactions with the surrounding residues, especially with the side chains of Phe5 and Cys45 and the main chain of Gly30. However, the inhibitor does not change the conformation of these residues except that Trp31 at the entrance of the hydrophobic channel moves slightly toward the inhibitor. Compared with native APLA2, the Ca2+-binding loop shows a little conformational change and a cation, probably Na+, occupies in the position of Ca2+. The binding of pBPB to APLA2 induce no other significant conformational changes in the enzyme molecule elsewhere.

Acetophenones↗
PubMed1998

Reduced prevalence of allergic disease in patients with multiple sclerosis is associated with enhanced IL-12 production.

BACKGROUND: We previously showed that the prevalence of allergic disease is decreased in patients with multiple sclerosis (MS); however, the mechanisms that explain this finding have not previously been defined. OBJECTIVES: We have demonstrated that protection of patients with MS from allergic disease may be caused by the production in monocytes from these patients of elevated quantities of IL-12 compared with that observed in monocytes from individuals with allergies. METHODS: Purified monocytes from peripheral blood of subjects with or without allergies and from individuals with MS were directly stimulated with Staphylococcus aureus Cowan strain I in the absence of T cells. IL-12 was quantitated by a sensitive reverse transcription, competitive PCR. RESULTS: IL-12 production was 5-fold greater in monocytes from patients with MS (n = 11) than that from individuals with allergies (n = 10) (for subjects with MS, 1.90+/-0.18 vs 1.24+/-0.19 log10 fmol/microL for individuals with allergies) (P = .02). Although the production of IL-12 in monocytes from patients with MS was slightly higher than that from subjects without allergies, this difference was not statistically significant. CONCLUSIONS: IL-12 production in individuals with MS is much greater than in individuals with allergies. Because IL-12 induces TH1 cytokine synthesis and reduces the production of TH2 cytokines, which amplify and prolong allergic inflammation, these studies suggest that enhanced IL-12 production may protect individuals with MS from the development of allergy but may predispose such individuals toward autoimmune inflammation in the central nervous system.

Adult↗
PubMed1998

A role for the cadherin family of cell adhesion molecules in hippocampal long-term potentiation.

The cadherins are a family of cell-cell adhesion molecules that mediate Ca2+-dependent homophilic interactions between cells and transduce signals by interacting with cytoplasmic proteins. In the hippocampus, immunostaining combined with confocal microscopy revealed that both neural- (N-) and epithelial- (E-) cadherin are present at synaptic sites, implying a role in synaptic function. Pretreatment of hippocampal slices with antibodies (Abs) raised against the extracellular domain of either N-cad or E-cad had no effect on basal synaptic properties but significantly reduced long-term potentiation (LTP). Infusion of antagonistic peptides containing the His-Ala-Val (HAV) consensus sequence for cadherin dimerization also attenuated LTP induction without affecting previously established LTP. Because the intense synaptic stimulation associated with LTP induction might transiently deplete extracellular Ca2+ and hence potentially destabilize cadherin-cadherin interactions, we examined whether slices could be protected from inhibition by N-cad Abs or HAV peptides by raising the extracellular Ca2+ concentration. Indeed, we found that high extracellular Ca2+ prevented the block of LTP by these agents. Taken together, these results indicate that cadherins are involved in synaptic plasticity, and the stability of cadherin-cadherin bonds may be regulated by synaptic stimulation.

Animals↗
PubMed1998

Electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry at 11.5 tesla: instrument design and initial results.

Initial results obtained using a new electrospray ionization (ESI) Fourier transform ion cyclotron resonance (FTICR) mass spectrometer operated at a magnetic field 11.5 tesla are presented. The new instrument utilized an electrostatic ion guide between the ESI source and FTICR trap that provided up to 5% overall transmission efficiency for light ions and up to 30% efficiency for heavier biomolecules. The higher magnetic field in combination with an enlarged FTICR ion trap made it possible to substantially improve resolving power and operate in a more robust fashion for large biopolymers compared to lower field instruments. Mass resolution up to 10(6) has been achieved for intermediate size biopolymers such as bovine ubiquitin (8.6 kDa) and bovine cytochrome c (12.4 kDa) without the use of frequency drift correction methods. A mass resolution of 370,000 has been demonstrated for isotopically resolved molecular ions of bovine serum albumin (66.5 kDa). Comparative measurements were made with the same spectrometer using a lower field 3.5-tesla magnet allowing the performance gains to be more readily quantified. Further improvements in pumping capacity of the vacuum system and efficiency of ion transmission from the source are expected to lead to further substantial sensitivity gains.

Algorithms↗
PubMed1998

Biosynthesis of the ansamycin antibiotic rifamycin: deductions from the molecular analysis of the rif biosynthetic gene cluster of Amycolatopsis mediterranei S699.

BACKGROUND: The ansamycin class of antibiotics are produced by various Actinomycetes. Their carbon framework arises from the polyketide pathway via a polyketide synthase (PKS) that uses an unusual starter unit. Rifamycin (rif), produced by Amycolatopsis mediterranei, is the archetype ansamycin and it is medically important. Although its basic precursors (3-amino-5-hydroxy benzoic acid AHBA, and acetic and propionic acids) had been established, and several biosynthetic intermediates had been identified, very little was known about the origin of AHBA nor had the PKS and the various genes and enzymes that modify the initial intermediate been characterized. RESULTS: A set of 34 genes clustered around the rifK gene encoding AHBA synthase were defined by sequencing all but 5 kilobases (kb) of a 95 kb contiguous region of DNA from A. mediterranei. The involvement of some of the genes in the biosynthesis of rifamycin B was examined. At least five genes were shown to be essential for the synthesis of AHBA, five genes were determined to encode the modular type I PKS that uses AHBA as the starter unit, and 20 or more genes appear to govern modification of the polyketide-derived framework, and rifamycin resistance and export. Putative regulatory genes were also identified. Disruption of the PKS genes at the end of rifA abolished rifamycin B production and resulted in the formation of P8/1-OG, a known shunt product of rifamycin biosynthesis, whereas disruption of the orf6 and orf9 genes, which may encode deoxysugar biosynthesis enzymes, had no apparent effect. CONCLUSIONS: Rifamycin production in A. mediterranei is governed by a single gene cluster consisting of structural, resistance and export, and regulatory genes. The genes characterized here could be modified to produce novel forms of the rifamycins that may be effective against rifamycin-resistant microorganisms.

Actinobacteria↗
PubMed1998

Melatonin reduces the increase in 8-hydroxy-deoxyguanosine levels in the brain and liver of kainic acid-treated rats.

In the present study, the effect of melatonin on oxidative DNA damage induced by kainic acid (KA) treatment was investigated. 8-hydroxy-deoxyguanosine (8-OH-dG) is a main product of oxidatively damaged DNA and was used as the endpoint in these studies. The levels of 8-OH-dG were found to be elevated in the hippocampus and frontal cortex of rats treated with KA. These elevated levels were significantly reduced in animals that were co-treated with melatonin. Thus, there was no difference in 8-OH-dG levels in the brain of control rats compared to those treated with KA (10 mg/kg) plus melatonin (10 mg/kg). The levels of 8-OH-dG also increased in the liver of rats treated with KA. This rise in oxidatively damaged DNA was also prevented by melatonin administration. Melatonin's ability to reduce KA-induced increases in neural and hepatic 8-OH-dG levels presumably relates to its direct free radical scavenging ability and possibly to other antioxidative actions of melatonin.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

Glutamine substitution at alanine1649 in the S4-S5 cytoplasmic loop of domain 4 removes the voltage sensitivity of fast inactivation in the human heart sodium channel.

Normal activation-inactivation coupling in sodium channels insures that inactivation is slow at small but rapid at large depolarizations. M1651Q/M1652Q substitutions in the cytoplasmic loop connecting the fourth and fifth transmembrane segments of Domain 4 (S4-S5/D4) of the human heart sodium channel subtype 1 (hH1) affect the kinetics and voltage dependence of inactivation (Tang, L., R.G. Kallen, and R. Horn. 1996. J. Gen. Physiol. 108:89-104.). We now show that glutamine substitutions NH2-terminal to the methionines (L1646, L1647, F1648, A1649, L1650) also influence the kinetics and voltage dependence of inactivation compared with the wild-type channel. In contrast, mutations at the COOH-terminal end of the S4-S5/D4 segment (L1654, P1655, A1656) are without significant effect. Strikingly, the A1649Q mutation renders the current decay time constants virtually voltage independent and decreases the voltage dependences of steady state inactivation and the time constants for the recovery from inactivation. Single-channel measurements show that at negative voltages latency times to first opening are shorter and less voltage dependent in A1649Q than in wild-type channels; peak open probabilities are significantly smaller and the mean open times are shorter. This indicates that the rate constants for inactivation and, probably, activation are increased at negative voltages by the A1649Q mutation reminiscent of Y1494Q/ Y1495Q mutations in the cytoplasmic loop between the third and fourth domains (O'Leary, M.E., L.Q. Chen, R.G. Kallen, and R. Horn. 1995. J. Gen. Physiol. 106:641-658.). Other substitutions, A1649S and A1649V, decrease but fail to eliminate the voltage dependence of time constants for inactivation, suggesting that the decreased hydrophobicity of glutamine at either residues A1649 or Y1494Y1495 may disrupt a linkage between S4-S5/D4 and the interdomain 3-4 loop interfering with normal activation-inactivation coupling.

Amino Acid Substitution↗
PubMed1998

Effect of prostaglandins on cyclic AMP production in cultured human ciliary muscle cells.

Prostaglandins (PGs) lower intraocular pressure by increasing uveoscleral outflow, presumably via a receptor-mediated mechanism coupled to a second messenger pathway in the ciliary muscle. In the present study, we examined the effect of prostanoids on cyclic AMP production in cultured human ciliary muscle cells. Cells were identified based on their expression of smooth muscle specific alpha-actin and monoclonal antibody against desmin. Cyclic AMP production in confluent cells incubated with buffer solution containing various concentrations of prostanoids was analyzed by radioimmunoassay. PGE2 caused a time-dependent increase in cyclic AMP concentrations which reached a maximum after 10 mins. With the exception of PGD2, all prostanoids produced a concentration-dependent increase in cyclic AMP levels with the following rank order of activity: PGE2 > 11-deoxy-PGE1 > 16,16-dimethyl PGE2 > sulprostone > PGF2alpha. PGE2-induced increase on cyclic AMP levels was unaffected by AH6809, an antagonist at both PGD2 (DP) and E2 (EP1) receptors. Flurbiprofen decreased basal cyclic AMP concentrations suggesting that intramurally-generated PGs stimulate the formation of the nucleotide in ciliary smooth muscle cells. PGE2-induced increases in cyclic AMP production was synergistic with those induced by the diterpene activator of adenylyl cyclase, forskolin. We conclude that prostanoids active at EP2-receptors can stimulate cyclic AMP production in cultured human ciliary muscle cells.

Adult↗
PubMed1998

Crystal structure of carboxypeptidase A complexed with an inactivator in two crystal forms.

Two different crystal forms of carboxypeptidase A (CPA) complexed with an inactivator were obtained by the method of hanging drop vapor diffusion. The inactivator, 2-benzyl-3-iodo-propanoic acid (BIPA), binds covalently to an active site residue Glu270 of CPA. The complexes were crystallized in the space group P2(1) (CPA-I) and P2(1)2(1)2(1) (CPA-II), respectively. The structures of both crystal forms were determined by molecular replacement using the native CPA crystal structure as the search model. The final crystallographic residuals are 0.163 for CPA-I and 0.152 for CPA-II. Except for the modification of Glu270, the inactivator exhibits normal binding mode compared with other ligand complexes of CPA. In the final electron density difference maps (2Fo-Fc, Fo-Fc), the density of the iodo ion could not be found in both crystal forms while the conserved water molecule remains coordinated to Zn2+ as in the native CPA. Comparisons of the complexes of CPA-BIPA with the native CPA and the CPA-D-Phe complex are presented. The mechanism of the inactivation of CPA and its implication for catalytic mechanism were discussed.

Animals↗
PubMed1998

Chemotherapy-induced apoptosis in melanoma cells is p53 dependent.

Metastatic melanomas are often resistant to chemotherapy. To study whether the p53 mutational status affects chemosensitivity, we compared the responses to chemotherapy of four melanoma cell lines containing the wild-type p53 and four cell lines carrying the mutant p53. Cisplatin, at 10 microM, virtually killed all the cells in the wild-type p53 cell lines, while 57-95% of the cells in the mutant p53 cell lines survived (P = 0.005). After treatment with 100 nM of vincristine, on average 18% of the wild-type p53 melanoma cells survived compared with 55% of the mutant p53 cells (P = 0.04). After treatment with 40 nM, 200 nM or 1 microM of camptothecin the survival rates were, on average, 16%, 8% and 4% for the wild-type p53 melanoma cells, compared with 89%, 67% and 38% for the mutant p53 cells, respectively (P = 0.00004, P = 0.003 and P = 0.04, respectively). The anticancer agents were not toxic to normal melanocytes at doses inducing cytotoxicity in wild-type p53 melanoma cells. The main mechanism of cytotoxicity appears to be drug-induced apoptosis. Cisplatin, camptothecin and vincristine all induced apoptosis in wild-type p53 melanoma cells, but not in mutant p53 cells. Our results suggest that chemotherapy-induced apoptosis in melanoma cells is p53 dependent, and mutation of the p53 gene is an indicator of drug resistance in melanoma.

Antineoplastic Agents↗
PubMed1998

Mechanisms of fibrinogen domains: biomaterial interactions.

Spontaneous adsorption of fibrinogen is critical to the pathogenesis of biomaterial-mediated inflammatory responses. However, the mechanism by which adsorbed fibrinogen affects phagocyte responses is still not clear. To investigate the molecular interaction between fibrinogen and biomaterials, fibrinogen fragments (D100 and E50) were generated and used in the present study. The results indicate that biomaterial: D100 interaction is essential to fibrinogen-mediated inflammatory responses, because biomaterials precoated with D100, but not E50, prompt strong inflammatory responses. Furthermore, the results from in vitro studies show that whole molecule fibrinogen and D100 exhibit very similar protein:surface interactions. Specifically: (1) both D100 and fibrinogen have high affinity for biomaterial surfaces; and (2) the retention rates of adsorbed D100 in both in vivo and in vitro environments are as high as that for adsorbed fibrinogen. On the other hand, E50 does bind to biomaterials but with low affinity because, once bound, it is not tightly adherent to the biomaterial surfaces. Taken together, the results suggest that the mechanism of fibrinogen-mediated inflammatory responses may involve the following three consecutive events: (1) after contact with blood or tissue fluid, the D domain tends to interact with biomaterial surfaces and is important in the tight binding of fibrinogen to implant surfaces; (2) the biomaterial surface then promotes conformational changes within the D domain, exposing P1 epitope (gamma 190-202, which interacts with phagocyte Mac-1 integrin); and (3) the engagement of Mac-1 integrin with P1 epitope then triggers subsequent phagocyte adherence and reactions.

Adsorption↗
PubMed1998

[Analysis of causes of revision after hip replacement].

From 1974 to 1991, two hundred and sixty-four cases of hip replacement were performed. These cases composed of 150 cases of artificial femoral head prosthesis replacement and 114 cases of total hip replacement. Fifteen cases were revised after the first replacement in 7.4 years average (5-16 years). The revision rate was 5.7%. The causes of revision were loose or subside of prosthesis, wear and tear of acetabulum, dislocation of artificial hip joint, etc, which caused pain and dysfunction. The revision cases were followed up for 4.7 years average with good result. To prevent revision, The medully canal shonld not be too wide and in osteoporosis cases, bone cement was suggested to apply. The chondrium of acetabulum should be removed completely.

Aged↗
PubMed1998

[Experimental study of homograft of repeated freezing-thawing treated and ultra-low-temperature treated tendon].

In order to compare the immunogenecity and biological properties of homologous tendon grafts after treatment from different methods of freezing, tendons from chickens received repeated freezing-thawing treatment or ultra-low-temperature treatment, and then, the post-treatment tendons were preserved in liquid nitrogen for 3 months before transplantation. The autogenous tendon transplantation was served as the control. It was found that in the group of repeated freezing-thawing treated tendons, the tendon cells all died and while in the ultra-low temperature treated tendons the active rate of tendon cells was 92.5% +/- 3.4%, and the histological observation showed that transplantation of frozen tendons would result in extensive infiltration of inflammatory cells in the grafted tendons and the peritendinous adhesion was serious than that of the autografts. The active flexion function, hydroxyproline levels and the biomechanical analysis showed no significant differences between the repeated freezing-thawing treated homografts and the ultra-low-temperature treated homografts, and that the autografts was definitely superior to the homografts. The conclusions were: (1) Transplantation of the homologous tendons from the two different methods of freezing could receive considerable success and there was no significant difference between them; (2) Transplantation of frozen homologous tendon graft might give successful result which was probably due to the preservation of the cellular activity of the tendon cells following freezing treatment and elimination of the antigen presenting cells in the tendon as well, and (3) Although the cellular components of the tendon were damaged and the antigenicity of the tendon was lowered, it did not necessarily mean that homologous tendon graft would always be successful in transplantation.

Animals↗
PubMed1998

[Relationship between IL-1 beta and TNF-alpha in subretinal fluids of rhegmatogenous retinal detachment with PVR].

The concentrations of IL-1 beta and TNF-alpha in subretinal fluids from 49 patients with rhegmatogenous retinal detachment with proliferative vitreoretinopathy(PVR) were measured by Enzyme-linked immunosorbent assay (ELISA). The results showed that all subretinal fluids contained IL-1 beta, their concentrations were positive correlation with severity of PVR (r = 0.677) and no correlation with age, sex, holes, ranges and times of retinal detachment, TNF-alpha was detected in 18/49 subretinal fluids including 2 patients with PVR-1 beta and 16 patients with PVR-C and the above cases. It suggested that IL-1 beta and TNF-a are involved in the pathogenesis of PVR.

Adolescent↗
PubMed1998

[Study of flow field uniformity downstream of mitral stenosis using Doppler echocardiography].

To research into the relationship between mitral lesion, stenosed degree and flow field uniformity downstream of mitral valve, we adopted the advanced color Doppler echocardiographic technique to conduct a quantitative study of flow field uniformity downstream of mitral valve in sixty patients with varying-degree of mitral stenosis in vivo. Twenty normal persons acted for comparison. The results showed that there was a linear correlation between the extent of valvular lesion, the stenosed degree and flow field uniformity downstream of mitral valve. We conclude that the more severe the mitral lesion is, the more grave the stenosis is and the worse the flow field uniformity is. This suggests that there might be a reciprocity between valvular lesion and flow field uniformity as well as turbulent shear stress, which should be further studied.

Adult↗
PubMed1998

[An autopsy analysis on 5 cases of poisoning death with tetramethylenedisulfotertramine].

Pathological changes due to intoxication of tetramethylenedisulphotetramine (TETS) were studied. The results showed that the signs of asphyxia were obvious, so were the congestion and edema of the brain. The spotty and focal hemorrhages in brain stems, multiple myolysis of papillary muscles and contractionbands necrosis of myocardium were observed occasionally. The main clinical symptom of intoxication was frequent clinic--tonic convulsions, which were similar to the grandma epilepsy. The poisoned died mainly in 3 hours. The general poisoning symptoms, LD50, toxicological mechanism and medicolegal expertise were also reviewed.

Adult↗
PubMed1998

[Determination of naftopidil and its main metabolite in plasma by high-performance liquid chromatography].

A method was developed for the determination of naftopidil (NAF) and its main metabolite desmethyl-naftopidil (DMN) in plasma by HPLC. A mixture of methanol, acetonitrile and 0.02 mol.L-1 K2HPO4 solution was used as mobile phase. Stationary phase was RP-C18. Propranolol was chosen as internal standard (IS), and the detector wavelength was 240 nm. Under these conditions, the retention times of IS, DMN and NAF were 6.2, 7.6 and 10.5 min respectively. Absolute recoveries from plasma were up to 93.4% (IS), 76.8% (DMN) and 80.2% (NAF). The assay was linear for DMN and NAF in the range of 10-800 ng.ml-1 plasma concentration, gamma = 0.9998. The lowest detection limits were 8 ng.ml-1 (DMN) and 5 ng.ml-1 (NAF), and the precisions within-day and day-to-day were no more than 6.3% for MDN and 11.6% for NAF. The drug concentration-time pattern of these two substances was also studied with this method. Result showed that naftopidil was quickly absorbed after p.o. and the concentration-time data were fitted to two compartment model, with half life (T1/2 beta) of 8.13 h.

Adrenergic alpha-Antagonists↗